Seroquel (generic name, quetiapine) is an atypical antipsychotic that made a tidy $4.4 billion for AstraZeneca last year. Seroquel’s golden goose status is based on a string of FDA approvals for schizophrenia, mania in bipolar disorder, and more recently, depression in bipolar disorder. In addition, it is commonly used off-label for insomnia, and the company is applying for FDA approval for the treatment of generalized anxiety disorder.
The drug’s approval for bipolar depression was particularly valuable, because it opened the door to off-label use in garden variety, unipolar depression—a much bigger market than bipolar depression. The problem is that the “BOLDER” studies, which formed the basis for FDA approval, had a glaring weakness. The patients who were enrolled were very different from the patients we see in clinical practice. The BOLDER studies excluded patients with:
--Current depression lasing longer than 12 months
--Substance use within 12 months
--Any other recently treated psychiatric disorders
In addition, any patients who had tried and not responded to two previous trials of antidepressants were not eligible for the study. This restriction is especially problematic, because by the time most real patients get the diagnosis of bipolar depression, they have already been on many rounds of antidepressants.
Thus, Seroquel is approved for a very special and unusual kind of depressed bipolar patient—someone who is who is unlikely to be seen by practicing psychiatrists. The patients I see are sicker and much more complex; prescribing Seroquel for them may or may not make them better, but is all but certain to cause significant weight gain, rendering them more vulnerable to heart disease and diabetes.
Which is all a very long-winded introduction to the latest scandal-in-the-making from AstraZeneca. As covered in BusinessWeek, and the Furious Seasons blog, AstraZeneca is being sued by thousands of patients who allege that the company hid information about Seroquel’s risk of weight gain and diabetes. 6,000 claims have been consolidated into a single case before a federal court in Orlando Florida.
Reams of documents have been shipped in by AstraZeneca related to the case, but none have been disclosed yet, because no actual trial has commenced. It is possible that in order to avoid disclosure of embarrassing documents, the company will settle the case and prevent a trial. But the news agency Bloomberg has filed a motion to force these documents to be unsealed, citing “the public's right of access to judicial documents."
Presumably, these documents will be just as damaging as the leaked Zyprexa documents which showed that Lilly’s “Viva Zyprexa” campaign deliberately encouraged primary care doctors to prescribe Zyprexa for unapproved uses.
Maybe more damaging, actually, because at least the Lilly documents did not involve a senior company scientist having sex with a company funded researcher and a ghostwriter. That’s right, folks—according to one publically available court document, the company’s lead research director, Wayne Macfadden, was getting awfully busy with women who did Seroquel research and wrote up the BOLDER results.
The document alleges that Macfadden's relationships with the women were "relevant and highly probative evidence of one high level AstraZeneca employee's determination to exploit his sexual relationships with these women in order to elevate Seroquel's status in the prescribing medical community through supposedly 'independent' publications of Seroquel safety and efficacy data….Moreover, the mere existence of these relationships calls into question the integrity of the scientific work product of those involved."
We don’t know if all these allegations are true, although Macfadden has already admitted to the dalliances.
At this point, AstraZeneca needs to do the right thing, which is to unseal the secret documents. Only then will the company be able to clear its name.